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Objectives Hypertensive encephalopathy in cats is an important entity but is underestimated in clinical practice. This could be explained, in part, by non-specific clinical signs. The objective of this study was to characterise the clinical manifestations of hypertensive encephalopathy in cats. Methods Cats with systemic hypertension (SHT) recognised by routine screening, associated with underlying predisposing disease or a clinical presentation suggestive of SHT (neurological or non-neurological), were prospectively enrolled over a 2-year period. Confirmation of SHT was based on at least two sets of measurements of systolic blood pressure >160 mmHg by Doppler sphygmomanometry. Results Fifty-six hypertensive cats with a median age of 16.5 years were identified; 31 had neurological signs. In 16/31 cats, neurological abnormalities were the primary complaint. The other 15 cats were first presented to the medicine or ophthalmology service, and neurological disease was recognised based on the cat’s history. The most common neurological signs were ataxia, various manifestations of seizures and altered behaviour. Individual cats also showed paresis, pleurothotonus, cervical ventroflexion, stupor and facial nerve paralysis. In 28/30 cats, retinal lesions were detected. Of these 28 cats, six presented with a primary complaint of visual deficits, and neurological signs were not the primary complaint; nine presented with non-specific medical issues, without suspicion of SHT-induced organ damage; in 13 cats, neurological issues were the primary complaint and fundic abnormalities were detected subsequently. Conclusions and relevance SHT is common in older cats and the brain is an important target organ; however, neurological deficits are commonly ignored in cats with SHT. Gait abnormalities, (partial) seizures and even mild behavioural changes should prompt clinicians to consider the presence of SHT. A fundic examination in cats with suspected hypertensive encephalopathy is a sensitive test to support the diagnosis.

Induced mutations are an essential source of genetic variation in plant breeding. EMS mutagenesis has been frequently applied, and mutants have been detected by phenotypic or genotypic screening of large populations. In this study, a rapeseed M2 population was derived from M1 parent cultivar “Express” treated with EMS. Whole genomes were sequenced from fourfold (4x) pools of 1,988 M2 plants representing 497 M2 families. Detected mutations were not evenly distributed and displayed distinct patterns across the 19 chromosomes with lower mutation rates towards the ends. Mutation frequencies ranged from 32/Mb to 48/Mb. On average, 284,442 single nucleotide polymorphisms per M2 DNA pool were found resulting from EMS mutagenesis. 55% were C→T and G→A transitions, characteristic for EMS induced (‘canonical’) mutations, whereas the remaining SNPs were ‘non-canonical’ transitions (15%) or transversions (30%). Additionally, we detected 88,725 high confidence insertions and deletions (InDels) per pool. On average, each M2 plant carried 39,120 canonical mutations, corresponding to a frequency of one mutation per 23.6 kb. Roughly 82% of such mutations were located either 5 kb upstream or downstream (~56%) of gene coding regions or within intergenic regions (26%). The remaining 18% were located within regions coding for genes. All mutations detected by whole-genome sequencing could be verified by comparison with known mutations. Furthermore, all sequences are accessible via the online tool “EMS Brassica” (http://www.emsbrassica.plantbreeding.uni-kiel.de/), which enables direct identification of mutations in any target sequence. The sequence resource described here will further add value for functional gene studies in rapeseed breeding.

Nerve root enlargement with increased contrast uptake has been reported in dogs and humans secondary to nerve root compression. In cats, nerve root enlargement and contrast uptake only have been reported in association with inflammatory and neoplastic diseases, but not as a sequela to nerve root compression. An 8‐year‐old oriental short hair cat was presented with acute neurologic deficits consistent with left‐sided sciatic nerve deficit and possible L6‐S1 myelopathy. Magnetic resonance imaging (MRI) was performed and identified compression of the cauda equina and L7 nerve root associated with intervertebral disc herniation (IVDH) at L6‐L7 as well as widespread sciatic nerve enlargement with moderate rim enhancement. A hemilaminectomy was performed to evacuate herniated disc material. The nerve root was biopsied and submitted for histological evaluation. Interstitial nerve edema was diagnosed. Follow‐up MRI 3 months postoperatively showed complete remission of the changes. Nerve root thickening together with contrast enhancement may represent nerve edema in cats secondary to IVDH.

Intraventricular tumors are rare, optimal treatment is not defined. Symptomatic patients often exhibit life-threatening hydrocephalus. With several months time-to-effect after radiotherapy (RT), increased intracranial pressure is concerning. This increase in pressure can be overcome by ventriculoperitoneal shunting (VPS).Retrospective evaluation of outcome and complications in dogs and cats with intracranial tumors treated with either RT or VPS/RT.Twelve client-owned cats and dogs.Dogs and cats with symptomatic intraventricular tumors treated with definitive-intent RT or VPS/RT were included in a retrospective, descriptive case series. Complications, tumor volume evolution, time-to-progression, and survival time were determined.Twelve animals were included: 1 cat and 5 dogs treated with single-modality RT and 4 cats and 2 dogs treated with VPS/RT. Neurological worsening seen in 4/6 animals during single-modality RT and 2/6 died during RT (suspected brain herniation). All dogs with VPS normalized clinically by the end of RT or earlier. Complications occurred in 4/6 animals, all but 1 were successfully managed surgically. Imaging follow-up in 8 animals surviving RT showed a marked decrease in tumor volume. Median survival time was 162 days (95% confidence interval [CI]: 16; infinity) for animals treated with RT and 1103 days (95%CI: 752; infinity) for animals treated with VPS/RT. Median time-to-progression was 71 days (95%CI: 7; infinity) and 895 days (95%CI: 704; infinity) for each group, respectively. Two dogs died because of intraventricular metastasis 427 and 461 days after single-modality RT.Ventriculoperitoneal shunting led to rapid normalization of neurological signs and RT had a measurable effect on tumor volume. Combination of VPS/RT seems to be beneficial.

Cortical atrophy has been identified using magnetic resonance imaging (MRI) in humans and dogs with Lafora disease (LD). In humans, proton magnetic resonance spectroscopy (1HMRS) of the brain indicates decreased N‐acetyl‐aspartate (NAA) relative to other brain metabolites. Brain 1HMRS findings in dogs with LD are lacking. A 6‐year‐old female Beagle was presented with a history of a single generalized tonic‐clonic seizure and episodic reflex myoclonus. Clinical, hematological, and neurological examination findings and 3‐Tesla MRI of the brain were unremarkable. Brain 1HMRS with voxel positioning in the thalamus was performed in the affected Beagle. It identified decreased amounts of NAA, glutamate‐glutamine complex, and increased total choline and phosphoethanolamine relative to water and total creatine compared with the reference range in healthy control Beagles. A subsequent genetic test confirmed LD. Abnormalities in 1HMRS despite lack of changes with conventional MRI were identified in a dog with LD.

Post-treatment outcome in canine glial tumours is described with a broad range of survival times between 2 and 28 months. After surgery or radiation therapy, the tumours may progress locally or spread within the central nervous system. It is unknown if tumour- or patient-specific factors influence prognosis. In humans, glioblastoma involving the subventricular zone has been found to recur distantly, with shortened time to progression and overall survival. We included 32 dogs irradiated for a presumptive primary glial brain tumour in this retrospective cohort study. Tumours were grouped relative to subventricular zone contact and overt ventricular invasion assessing pre-treatment magnetic resonance images. Median time to progression (TTP) for all cases was 534 days (95%CI, 310–758), with a significantly shorter TTP in dogs with lesions at the subventricular zone (median TTP, 260 vs. 687 days; p=.049). Tumours at the subventricular zone progressed more often (p=.001), and more likely as CNS-metastasis (52.9% vs. 13.3%, p=.028). Median overall survival (OS) was 489 days (95%CI, 147–831) and median tumour-specific survival 609 days (95%CI, 382–835). Involvement of the subventricular zone was significantly associated with a shorter tumour-specific survival (median, 306 vs. 719 days; p=.044). Glial tumours contacting the subventricular zone in dogs have a shorter tumour-specific survival and a higher rate of progression and CNS-metastasis. Despite local tumour control, metastasis must be considered and should prompt further treatment approaches.

Background: Little is known about idiopathic Epilepsy in Greater Swiss Mountain Dogs. Until now this breed is not listed as a predisposed breed for idiopathic epilepsy. The aim of this study was to estimate the prevalence of idiopathic epilepsy in Greater Swiss Mountain Dogs in Switzerland and to describe the clinical characteristics of epilepsy in this breed including seizures semiology and response to treatment. Material and Methods: Records of the Swiss Kennel Club for Greater Swiss Mountain Dogs were searched for reported cases of epileptic seizures between 1999-2019. The total number of reported cases and the signalment was reviewed. Furthermore, all owners of Greater Swiss Mountain Dogs registered to the breeding club were invited to complete an online questionnaire. Results: In total 600 Greater Swiss Mountain Dog's live in Switzerland: 70-90 puppies are born each year. Between 1999 and 2019 34 dogs (2%) were announced with seizures. Of the 400 owners invited to answer the questionnaire 128 completed the questionnaire. 20 of these 128 dogs were suffering from idiopathic epilepsy. The prevalence for idiopathic epilepsy based on the questionnaire was therefore 15,6%. All affected dogs showed generalized tonic-clonic seizures. Cluster seizures and status epilepticus occurred in 5 (41,6%) and 6 (50%) of the dogs. Long term seizure control was only achieved in 10% of the dogs. Five dogs (25%) died or were euthanized because of insufficient seizure control. Only one dog (5%) showed clinical remission. Conclusion: Prevalence of idiopathic epilepsy is higher in Greater Swiss Mountain Dogs in Switzerland compared to the general dog population. Seizure control seems to be difficult to achieve in this breed and remission-rate is low.Hintergrund: Bisher wird der Grosse Schweizer Sennenhund nicht unter den prädisponierten Rassen für idiopathische Epilepsie geführt. Allerdings liegen hierzu bisher auch nur wenige Daten und keine wissenschaftlichen Studien vor. Ziel dieser Studie ist es, die Häufigkeit der idiopathischen Epilepsie bei Grossen Schweizer Sennenhunden zu erheben und Anfallscharakteristik, Therapieprotokolle und -erfolge bei den betroffenen Hunden zu dokumentieren, um das Risiko für diese Erkrankung und den Verlauf besser einschätzen zu können. Material und Methoden: Es wurden Unterlagen des Schweizer Zuchtverbandes «Klub für Grosse Schweizer Sennenhunde» mit gemeldeten Fällen von epileptischen Anfällen ab Geburtsjahr 1999–2019 analysiert. Zusätzlich wurde eine Einladung zu einer Online-Umfrage zur idiopathischen Epilepsie (Einteilung Anfälle ja/nein, wenn ja; Angaben zu Anfallscharakteristik, Therapie, Therapieerfolge) an die Mitglieder des Zuchtverbandes verschickt. Ergebnisse: In der Schweiz besteht die Population aus ca. 600 Tieren, 70–90 Welpen werden pro Jahr geboren. Im Zeitraum zwischen 1999 und 2019 wurden dem Zuchtverband 34 Hunde mit Epilepsie in der Schweiz gemeldet, das entspricht einer Rate von an Epilepsie erkrankten Hunden von ca. 2%. 400 Tierbesitzer wurden zur Umfrage eingeladen und 128 nahmen teil. Die Prävalenz von idiopathischer Epilepsie beim Grossen Schweizer Sennenhund betrug mit 20 erkrankten Hunden 15,6%. Alle betroffenen Tiere zeigten generalisierte tonisch-klonische Anfälle. Bei 5 Tieren (41,6%) trat ein Status epilepticus auf. Bei 6/12 (50%) Hunden traten Clusteranfälle auf. Andauernde Therapieerfolge wurden nur bei 10% erzielt, 25% sind verstorben und Remission wurde ausschliesslich bei einem Hund (5%) erreicht. Schlussfolgerungen: Die Prävalenz der idiopathischen Epilepsie in Grossen Schweizer Sennenhunden in der Schweiz ist höher als in der durchschnittlichen Hundepopulation (0,6–0,75%). Status epilepticus und Clusteranfälle sind häufig, eine Remission ist sehr selten.Contexte: On sait peu de choses sur l’épilepsie idiopathique chez les Grands Bouviers Suisses. Jusqu’à présent, cette race n’est pas répertoriée comme une race prédisposée à l’épilepsie idiopathique. Le but de cette étude était d’estimer la prévalence de l’épilepsie idiopathique chez les Grands Bouviers Suisses en Suisse et de décrire les caractéristiques cliniques de l’épilepsie chez cette race, y compris la sémiologie des crises et la réponse au traitement. Matériel et méthodes: Les archives de l’association d’élevage «Club des Grands Bouviers Suisses» ont été étudiées pour les cas signalés de crises d’épilepsie entre 1999 et 2019. Le nombre total de cas signalés et le signalement ont été examinés. De plus, tous les propriétaires de Grands Bouviers Suisses inscrits au club d’élevage ont été invités à remplir un questionnaire en ligne. Résultats: Au total 600 Grands Bouviers Suisses vivent en Suisse et 70 à 90 chiots naissent chaque année. Entre 1999 et 2019, 34 chiens (2%) ont fait l’objet de crises d’épilepsie. Sur les 400 propriétaires invités à répondre au questionnaire, 128 ont rempli le questionnaire. 20 de ces 128 chiens souffraient d’épilepsie idiopathique. La prévalence de l’épilepsie idiopathique sur la base du questionnaire était donc de 15,6%. Tous les chiens atteints ont présenté des crises tonico-cloniques généralisées. Chez 5 animaux (41,6%) un status epilepticus est survenu et des crises en série chez 6 animaux (50%). Le contrôle à long terme des crises n’a été obtenu que chez 10% des chiens. Cinq chiens (25%) sont morts ou ont été euthanasiés en raison d’un contrôle insuffisant des crises. Un seul chien (5%) a présenté une rémission clinique. Conclusion: La prévalence de l’épilepsie idiopathique est plus élevée chez les Grands Bouviers Suisses en Suisse que dans la population canine générale. Le contrôle des crises semble difficile à réaliser dans cette race et le taux de rémission est faible.Stato dell’arte: L’epilessia idiopatica del grande bovaro svizzero è stata finora poco investigata. Attualmente questa razza non è inclusa nelle razze predisposte all’epilessia idiopatica. Lo scopo di questo studio è di investigare la prevalenza dell’epilessia idiopatica nel grande bovaro svizzero in una popolazione svizzera e descrivere le caratteristiche cliniche di questa patologia in questa razza canina includendo la semeiotica delle crisi epilettiche e la risposta clinica alla terapia. Materiali e metodi: le storie cliniche dei grandi bovari svizzeri iscritti al club cinofilo svizzero sono state ricercate in un intervallo temporale compreso tra il 1999–2019 al fine di segnalare casi affetti da epilessia idiopatica. Sono stati esaminati il numero totale dei casi e il relativo segnalamento. Inoltre, tutti i proprietari del grande bovaro svizzero registrati in allevamenti ufficiali sono stati invitati a compilare un questionario online. Risultati: in totale in Svizzera sono registrati 600 soggetti di grande bovaro svizzero: ogni anno nascono tra i 70 ed i 90 cuccioli. Tra il 1999 e il 2019 sono stati segnalati 34 soggetti (2%) affetti da crisi epilettiche. Il questionario online è stato compilato da 128 su 400 proprietari contattati. Venti proprietari su 128 hanno segnalato la presenza di crisi epilettiche di natura idiopatica. La relativa prevalenza dell’epilessia idiopatica riscontrata è risultata, dunque, pari al 15,6% basandosi sui dati derivati dal questionario. Tutti i soggetti affetti presentavano crisi epilettiche di tipo tonico-clonico. Cinque soggetti (41,6%) sono stati affetti da status epilepticus. Sei soggetti su dodici (50%) hanno presentato crisi di tipo cluster. Il controllo a lungo termine delle crisi è stato possibile solo nel 10% dei casi. Cinque soggetti (25%) sono deceduti, un solo soggetto (5%) ha presentato remissioni dei sintomi clinici. Conclusioni: la prevalenza dell’epilessia idiopatica nel grande bovaro svizzero in Svizzera è più grande se confrontata con quella generale nella popolazione canina. Lo stato epilettico e le crisi di tipo cluster sono comuni in questa razza, mentre la percentuale di soggetti che recuperano dai sintomi clinici è bassa.

Bilateral carotid artery ligation has been reported as a lifesaving procedure to control severe hemorrhage. However, reports are sparse and little information is available regarding the potential risks associated with this procedure. We report an ischemic brain infarct as a complication after vascular surgery. A 3-year old, male intact border collie was presented for acute onset of forebrain signs 5 days after bilateral carotid artery ligation. Multimodal brain MRI including morphologic sequences, MR angiography, diffusion- and perfusion-weighted images were performed. MRI revealed a well-defined intra-axial lesion of the left caudate nucleus, with increased T2 and decreased T1 signal intensity and moderate heterogeneous peripheral contrast enhancement. The cerebral blood flow was reduced relative to the contralateral caudate nucleus. Images were consistent with a subacute lacunar ischemic infarct of the left striate artery. Additionally, multiple arterio-arterial anastomosis arising from the vertebral arteries were visible in the angiography sequences. Ischemic infarct due to thromboembolism should be considered as a possible complication associated with bilateral carotid artery ligation. Collateral blood supply can develop as early as 5 days after surgery.

Resting-state functional Magnetic Resonance Imaging (rs-fMRI) has become an established technique in humans and reliably determines several resting state networks (RSNs) simultaneously. Limited data exist about RSN in dogs. The aim of this study was to investigate the RSNs in 10 healthy beagle dogs using a 3 tesla MRI scanner and subsequently perform group-level independent component analysis (ICA) to identify functionally connected brain networks. Rs-fMRI sequences were performed under steady state sevoflurane inhalation anaesthesia. Anaesthetic depth was titrated to the minimum level needed for immobilisation and mechanical ventilation of the patient. This required a sevoflurane MAC between 0.8 to 1.2. Group-level ICA dimensionality of 20 components revealed distributed sensory, motor and higher-order networks in the dogs’ brain. We identified in total 7 RSNs (default mode, primary and higher order visual, auditory, two putative motor-somatosensory and one putative somatosensory), which are common to other mammals including humans. Identified RSN are remarkably similar to those identified in awake dogs. This study proves the feasibility of rs-fMRI in anesthetized dogs and describes several RSNs, which may set the basis for investigating pathophysiological characteristics of various canine brain diseases.

Background Relapses in steroid-responsive meningitis-arteritis (SRMA) are frequently observed but specific treatment protocols to address this problem are sparsely reported. Standard treatment includes prolonged administration of glucocorticoids as monotherapy or in combination with immunosuppressive drugs. The aim of this study was to assess the safety and efficacy of cytosine arabinoside (CA) in combination with glucocorticoids for treatment of SRMA relapses in 12 dogs on a retrospective basis. Methods Dogs with recurrent episodes of SRMA and treated with a combination of CA and prednisolone were included. Information about clinical course, treatment response and adverse events was collected from medical records. Ethical approval was not required for this study. Results Ten dogs (10/12) responded well to the treatment with clinical signs being completely controlled. One dog is in clinical remission, but still under treatment. One dog (8%) showed further relapse. Mean treatment period was 51 weeks. Adverse events of variable severity (grade 1–4/5) were documented in all dogs during treatment according to the veterinary cooperative oncology group grading. Three dogs developed severe adverse events. Laboratory findings showed marked changes up to grade 4. Diarrhoea and anaemia were the most often observed adverse events (6), followed by dermatitis (4), alopecia (3) and pneumonia (3). Including blood chemistry changes (13), 50 adverse events were found in total. Conclusion Treatment with CA and glucocorticoids resulted in clinical remission in 10/12 dogs, but a high incidence of adverse events occurred requiring additional measures. All adverse events could be managed successfully in all cases.

A 17-month-old Warmblood filly was referred to our clinic for evaluation of congenital facial nerve (FN) paralysis. Clinical examination revealed a right-sided facial paralysis with mild masticatory muscle atrophy, mild dysphagia and exposure keratitis. Apart from the FN deficits, neurological examination of the remaining cranial nerves showed no abnormalities. Magnetic resonance imaging (MRI) examination using a 3.0 Tesla scanner showed that in comparison to the left FN, the intracranial section of the right FN between the pons and internal acoustic canal was thinner, whereas it appeared indistinct and thickened within the internal acoustic canal and facial canal. Signs of meningitis or encephalitis were not present on MRI. Cerebrospinal fluid analysis showed mild pleocytosis. The owner of the filly requested euthanasia due to the guarded prognosis. At necropsy, the intracranial section of the right FN was macroscopically thinner than the left side and within the facial canal, a 5 mm tissue stump could be identified with an absent extracranial part of the right FN. Histological examination of the brain stem showed different architecture of the left and right motor nuclei of the FN: in the left nucleus, motor neurons of a normal size and well stainable Nissl bodies were present, whereas in the right nucleus, neurons with Nissl bodies were decreased in number and size. Further, a cytoplasmic rich cell population with a nucleus size compatible with normal neurons was present. These cells were suspected to be atrophic neurons. The tissue stump within the facial canal was histologically identified as connective tissue. Unilateral malformation of the FN has not previously been described in the horse. This filly showed a right-sided, intracranial hypoplasia accompanied by an extracranial aplasia of the FN causing complete, congenital facial nerve paralysis, which corresponded to a difference in the architecture of the affected motor nucleus of the FN.

Purpose: This phase III study compared the efficacy and safety of proposed biosimilar MYL-1402O with reference bevacizumab (BEV), as first-line treatment for patients with stage IV non-squamous non-small-cell lung cancer. Patients and methods: Patients were randomly assigned (1:1) to receive MYL-1402O or bevacizumab with carboplatin-paclitaxel up to 18 weeks (6 cycles), followed by up to 24 weeks (8 cycles) of bevacizumab monotherapy. The primary objective was comparison of overall response rate (ORR), based on independently reviewed best tumor responses as assessed during the first 18 weeks. ORR was analyzed per US Food and Drug Administration (ratio of ORR) and European Medicines Agency (difference in ORRs) requirements for equivalence evaluation. Secondary end points included progression-free survival, disease control rate, duration of response, overall survival, safety, and immunogenicity over a period of 42 weeks, and pharmacokinetics (up to 18 weeks). Results: A total of 671 patients were included in the intent-to-treat population. The ratio of ORR was 0.96 [confidence interval (CI) 0.83, 1.12] and the difference in ORR was −1.6 (CI −9.0, 5.9) between treatment arms; CIs were within the predefined equivalence margins. Overall, the incidence of treatment-emergent adverse events and serious adverse events was comparable. Treatment-emergent anti-drug antibody (ADA) positivity was transient, with no notable differences between treatment arms (6.5% versus 4.8% ADA positivity rate in MYL-1402O versus BEV, respectively). The incidence of neutralizing antibody post-baseline was lower in the MYL-1402O arm (0.6%) compared to the bevacizumab arm (2.5%). Conclusions: MYL-1402O is therapeutically equivalent to bevacizumab, based on the ORR analyses, with comparable secondary endpoints. Trial Registry Information EU Clinical Trials Register, Registration # EudraCT no. 2015-005141-32 https://www.clinicaltrialsregister.eu/ctr-search/search?query=2015-005141-32 Plain language summary Previous studies established bioequivalence of the proposed bevacizumab biosimilar MYL-1402O to reference bevacizumab. In this randomized, double-blind, phase III trial, MYL-1402O ( n = 337) demonstrated comparable efficacy to bevacizumab ( n = 334) in treating advanced non-squamous non-small-cell lung cancer per Food and Drug Administration and European Medicines Agency requirements for equivalence; the ratio of objective response rate (ORR) was 0.96 [90% confidence interval (CI) 0.83, 1.12] and the difference in ORR (MYL-1402O:bevacizumab) was −1.6 (95% CI −9.0, 5.9). Median progression-free survival at 42 weeks was comparable: 7.6 (7.0, 9.5) with MYL-1402O versus 9.0 (7.2, 9.7) months ( p = 0.0906) with bevacizumab, by independent review. Treatment-emergent adverse events leading to death (2.4% vs 1.5%), serious adverse events (17.6% vs 16.7%), and antidrug antibodies (6.5% vs 4.8%), were comparable in the MYL-1402O vs bevacizumab arms, respectively. The incidence of neutralizing antibody post-baseline was lower with MYL-1402O (0.6%) than with bevacizumab (2.5%). These findings confirm therapeutic equivalence of MYL-1402O to bevacizumab, providing opportunities for improving access to bevacizumab.

In vivo diagnosis of tick-borne encephalitis is difficult due to high seroprevalence and rapid viral clearance, limiting detection of antibodies in blood and cerebrospinal fluid. Magnetic resonance imaging (MRI) characteristics of tick-borne encephalitis have been reported, however MRI studies can also be negative despite the presence of neurologic signs. Magnetic resonance spectroscopy (1 H MRS) is an imaging method that provides additional information about the metabolic characteristics of brain tissues. The purpose of this retrospective cross-sectional study was to describe brain metabolites using short echo time single-voxel 1 H MRS in dogs with confirmed tick-borne encephalitis and compare them with healthy dogs. Inclusion criteria for the affected dogs were neurological symptoms suggestive of tick-borne encephalitis, previous endemic stay and tick-bite, diagnostic quality brain MRI and 1 H MRS studies, and positive antibody titers or confirmation of tick-borne encephalitis with necropsy. Control dogs were 10, clinically normal beagles that had been used in a previous study. A total of six affected dogs met inclusion criteria. All dogs affected with tick-borne encephalitis had 1 H MRS metabolite concentration alterations versus control dogs. These changes included mild to moderate decreases in N-acetyl aspartate and creatine peaks, and mild increases in glutamate/glutamine peaks. No lactate or lipid signal was detected in any dog. Myoinositol and choline signals did not differ between affected and control dogs. In conclusion, findings supported the use of 1 H MRS as an adjunctive imaging method for dogs with suspected tick-borne encephalitis and inconclusive conventional MRI findings.

OBJECTIVES The aim of this study was to perform exploratory analyses of the efficacy and safety of pancrelipase delayed-release capsules (Creon) in patients with exocrine pancreatic insufficiency (EPI) with (n = 36) and without (n = 18) concurrent diabetes mellitus (DM). METHODS This was a retrospective, post hoc, subgroup (±DM) analysis of a double-blind, randomized, placebo-controlled trial of pancrelipase in patients with EPI due to chronic pancreatitis or pancreatectomy (total or partial). After a 5-day placebo run-in period (baseline), patients were randomized to pancrelipase (72,000 lipase units/meal, 36,000/snack) or placebo for 7 days. Outcomes included changes in coefficients of fat absorption (CFA) and nitrogen absorption (CNA) from baseline to the end of the double-blind period. RESULTS Mean changes in nutrient absorption were greater with pancrelipase versus placebo in patients with DM (CFA, 36.0% vs 7.5%, P < 0.0001; CNA, 33.4% vs 3.7%, P = 0.0002) and without DM (CFA, 25.2% vs 12.3%, P = 0.0326; CNA, 39.1% vs 17.6%, P = 0.1187). Diabetes mellitus was not significantly associated with outcomes for CFA (P = 0.0802) and CNA (P = 0.2934). Incidences of adverse events, including hypoglycemia and hyperglycemia, were similar in the pancrelipase and placebo arms. CONCLUSIONS Pancrelipase improved fat and protein absorption in patients with EPI due to chronic pancreatitis or pancreatectomy, with or without DM, and matched the safety profile previously reported.

OBJECTIVE To investigate metabolite concentrations of the brains of dogs with intracranial neoplasia or noninfectious meningoencephalitis by use of short echo time, single voxel proton magnetic resonance spectroscopy (1H MRS) at 3.0 T. ANIMALS 29 dogs with intracranial lesions (14 with neoplasia [3 oligodendromas, 3 glioblastomas multiformes, 3 astrocytomas, 2 lymphomas, and 3 meningiomas] and 15 is with noninfectious meningoencephalitis) and 10 healthy control dogs. PROCEDURES Short echo time, single voxel 1H-MRS at 3.0 T was performed on neoplastic and noninfectious inflammatory intracranial lesions identified with conventional MRI. Metabolites of interest included N-acetyl aspartate (NAA), total choline, creatine, myoinositol, the glutamine-glutamate complex (Glx), glutathione, taurine, lactate, and lipids. Data were analyzed with postprocessing fitting algorithm software. Metabolite concentrations relative to brain water content were calculated and compared with results for the healthy control dogs, which had been previously evaluated with the same 1H MRS technique. RESULTS NAA, creatine, and Glx concentrations were reduced in the brains of dogs with neoplasia and noninfectious meningoencephalitis, whereas choline concentration was increased. Concentrations of these metabolites differed significantly between dogs with neoplasia and dogs with noninfectious meningoencephalitis. Concentrations of NAA, creatine, and Glx were significantly lower in dogs with neoplasia, whereas the concentration of choline was significantly higher in dogs with neoplasia. Lipids were predominantly found in dogs with high-grade intra-axial neoplasia, meningioma, and necrotizing meningoencephalitis. A high concentration of taurine was found in 10 of 15 dogs with noninfectious meningoencephalitis. CONCLUSIONS AND CLINICAL RELEVANCE 1H MRS provided additional metabolic information about intracranial neoplasia and noninfectious meningoencephalitis in dogs.

Case summary A 10-year-old castrated male domestic shorthair cat was referred for surgical treatment of a left-sided frontal lobe meningioma diagnosed by CT. Clinically, the cat had generalised tonic–clonic seizures, which reduced in frequency after treatment was started with prednisolone. After definition of the anatomical landmarks of the feline skull, a bilateral transfrontal craniotomy allowed en bloc removal of the meningioma. While postoperative recovery was uneventful, right-sided proprioceptive deficits were still present 6 months after surgery. MRI detected a probable meningoencephalocele herniating through the surgical bone defect in the frontal sinus. Because of the mild neurological deficits and good quality of life, the meningoencephalocele was not treated. Thirty-one months after meningioma removal the cat was alive without further neurological progression. Relevance and novel information To our knowledge, this is the first report to describe, in detail, the technique of transfrontal craniotomy in cats. Iatrogenic meningoencephalocele is a complication that has not previously been described after meningioma removal in cats, and should be considered as a potential complication after craniotomy.

Pegfilgrastim is indicated for reducing the duration of neutropenia and incidence of febrile neutropenia in patients receiving cytotoxic chemotherapy. Here, safety and efficacy of MYL-1401H, a proposed pegfilgrastim biosimilar, were investigated as prophylaxis for chemotherapy-induced neutropenia. This was a phase 3, multicenter, randomized, double-blind, parallel-group equivalence trial of MYL-1401H vs European Union–sourced reference pegfilgrastim. Patients with newly diagnosed stage II/III breast cancer eligible to receive (neo) adjuvant chemotherapy with docetaxel/doxorubicin/cyclophosphamide every 3 weeks for 6 cycles were enrolled and randomized 2:1 to 6 mg of MYL-1401H or reference pegfilgrastim 24 h (+ 2-h window after the first 24 h) after the end of chemotherapy. The primary efficacy endpoint was the duration of severe neutropenia in cycle 1 (i.e., days with absolute neutrophil count (ANC)

Nemaline myopathy (NM) is a congenital neuromuscular disorder with heterogeneous clinical signs such as muscle weakness, affecting humans, seldom dogs and cats. For human NM, several causative gene mutations have been identified. The hallmark of this disease is the presence of sarcoplasmic inclusions (nemaline rods) in skeletal muscle fibres, which can be visualised in sections of muscle specimens. Ultrastructurally, an enlargement and streaming of the Z lines can be detected. Here, the case of two 10-week-old female Border collie littermates with progressive gait dysfunction, muscle stiffness and exercise intolerance, which were euthanased because of poor prognosis, is described. Histology of formalin-fixed paraffin-embedded muscle samples revealed sarcoplasmic rods visible in tissue sections stained with haematoxylin and eosin, the Gomori trichrome and the phosphotungstic acid haematoxylin stain. In electron microscopy, the rods were confirmed as streaming of the Z lines. Therefore, a congenital NM was diagnosed.

Corpus callosum abnormalities (CCA) rarely occur in dogs and are related to hypo/adypsic hypernatremia and seizures. Hypoplasia and dysplasia of the corpus callosum (CC) with concomitant lobar holoprosencephaly is the most common variant. It is currently uncertain using conventional MRI if canine CCA reflects the failure of commissural fibers to develop or the failure of the commissural fibers to cross hemispheres. Diffusion tensor imaging was performed in a 4-year-old Staffordshire mix breed dog with CCA and an age-matched healthy Beagle. In comparison to the control dog, CC tractography of the affected dog depicted only axonal tracts corresponding to the temporal CC fibers. The cingulum bundles appeared supernumerary with unorganized architecture, extending into the ipsilateral cerebral cortex, and therefore strongly suggested homology to Probst bundles reported in humans with CCA. The presence of Probst bundles in canine CCA could represent compensatory neuroplasticity-mediated networking and may contribute the fair prognosis reported in affected dogs.

Background Use of strongly hypofractionated radiation treatments in dogs with intracranial neoplasia did not improve outcomes and yielded increased rates of toxicosis. Objectives To evaluate safety and efficacy of a new, moderately hypofractionated radiation protocol of 10 × 4 Gy compared to a standard protocol. Animals Convenience sample of 56 client-owned dogs with primary symptomatic brain tumors. Methods Retrospective observational study. Twenty-six dogs were assigned to the control standard protocol of 20 × 2.5 Gy (group A) and 30 dogs to the new protocol of 10 × 4 Gy (group B), assigned on owners' informed consent. Statistical analysis was conducted under the "as treated" regime, using Kaplan-Meier and Cox-regression analysis. Treatment was delivered with technically advanced image-guided radiation therapy. The 2 treatment groups were compared in terms of outcome and signs of toxicosis. Results Overall progression-free interval (PFI) and overall survival (OS) time were favorable, with 663 (95%CI: 497;828) and 637 (95%CI: 403;870) days, respectively. We found no significant difference between the two groups: PFI for dogs in group A vs B was 608 (95%CI: 437;779) days and mean (median not reached) 863 (95%CI: 644;1083) days, respectively (P = .89), and OS for dogs in group A vs B 610 (95%CI: 404;816) and mean (median not reached) 796 (95%CI: 586;1007) days (P = .83). Conclusion and clinical importance In conclusion, 10 × 4 Gy is a safe and efficient protocol for treatment of primary intracranial neoplasia and future dose escalation can be considered.

Winter oilseed rape (Brassica napus L.) cultivation causes high nitrogen (N) balance surpluses. The breeding and cultivation of N-efficient cultivars (high grain yield under low N supply) can contribute to the reduction of the crop-specific N surpluses. Comparing line cultivars with hybrids and dwarfs the hypothesis was tested if stay-green into reproductive growth contributes to superior N efficiency of hybrids and dwarfs. The present work comprised two years field experiments with ten line, five hybrid and three dwarf cultivars and hydroponic experiments with three hybrid and nine line cultivars. Hybrids were superior in yield formation independent of the N supply. The greater N efficiency of the hybrids was related to a higher N uptake until maturity, but not to stay-green. This was in agreement with a hydroponic experiment in which the hybrids were particularly responsive in N starvation-induced leaf senescence of older leaves as revealed by SPAD, photosynthesis and the expression of the senescence-specific cysteine protease gene SAG12-1. Additionally, hybrids were characterized by an efficient N retranslocation from vegetative to reproductive plant organs in combination with a lower grain-N concentration. Both, N uptake and N utilization efficiency were decisive for the superior N efficiency of the hybrids.

Simvastatin and fenofibrate are frequently co-prescribed at staggered intervals for the treatment of dyslipidemia. Since a drug-drug interaction has been reported when the two drugs are given simultaneously, it is of clinical interest to know whether the interaction differs between simultaneous and staggered combinations. A study, assessing the impact of both combinations on the interaction, was conducted with 7-day treatment regimens using simvastatin 40 mg and fenofibrate 145 mg: (A) simvastatin only (evening), (B) simvastatin and fenofibrate (both in evening), and (C) simvastatin (evening) and fenofibrate (morning). Eighty-five healthy subjects received the respective treatments in a randomized, 3-way cross-over study. The pharmacokinetics of simvastatin and the active metabolite simvastatin acid were determined. There was a limited reduction in the AUC0-24h of simvastatin acid of 21 and 29% for simultaneous and staggered combination, respectively. The geometric mean AUC0-24h ratio of simvastatin acid for the two combined dosing regimens (B/C) and 90% confidence interval were 111% (102-121). The interaction apparently had no impact on lipid markers. The findings imply that the observed pharmacokinetic interaction is unlikely clinically relevant, and support the combined use of simvastatin and fenofibrate not only given at staggered interval but also given simultaneously.

Eighteen Mn complexes with N-donor and carboxylate ligands have been synthesized and characterized. Three Mn complexes among them are new and are reported for the first time. The reactions of oxygen evolution in the presence of oxone (2KHSO5·KHSO4·K2SO4) and cerium(iv) ammonium nitrate catalyzed by these complexes are studied and characterized by UV-visible spectroscopy, X-ray diffraction spectrometry, dynamic light scattering, Fourier transform infrared spectroscopy, electron paramagnetic resonance spectroscopy, transmission electron microscopy, scanning electron microscopy, membrane-inlet mass spectrometry and electrochemistry. Some of these complexes evolve oxygen in the presence of oxone as a primary oxidant. CO2 and MnO4(-) are other products of these reactions. Based on spectroscopic studies, the true catalysts for oxygen evolution in these reactions are different. We proposed that for the oxygen evolution reactions in the presence of oxone, the true catalysts are both high valent Mn complexes and Mn oxides, but for the reactions in the presence of cerium(iv) ammonium nitrate, the active catalyst is most probably a Mn oxide.

Objectives This study aimed to determine whether the efficacy of pancrelipase/pancreatin (CREON®) may be affected by the concomitant use of proton pump inhibitors (PPIs)/histamine-2 receptor antagonists (H2RAs). Methods An analysis of integrated data from all clinical trials of pancrelipase/pancreatin supported by Abbott (34 trials, 1142 unique subjects) was conducted. All trials included patients with pancreatic exocrine insufficiency, and most cases were associated with cystic fibrosis, chronic pancreatitis, or pancreatic surgery. Study designs included single and double blind, open label, parallel group, and crossover, and most were randomized. The primary end point for this analysis was on-treatment coefficient of fat absorption (CFA) according to concomitant PPI/H2RA use (yes/no). Results There were no meaningful differences in mean CFA values at the end of pancrelipase/pancreatin treatment by concomitant PPI/H2RA use: yes (n = 254), 82.7% versus no (n = 449), 84.2%. No meaningful differences were observed when the same analysis was carried out by disease type (cystic fibrosis, chronic pancreatitis, and pancreatic surgery). Conclusions This analysis of data from clinical trials enrolling patients with pancreatic exocrine insufficiency suggests that the efficacy of pancrelipase/pancreatin is not affected by concomitant PPI/H2RA use, as determined by end-of-treatment CFA values, and supports the treatment guidelines' recommendation that acid suppression is not routinely required with pancreatic enzyme replacement therapy.

A 2-month-old female goat was presented for depressed mental status and multifocal central neurologic signs 3 weeks after hot-iron disbudding. Conventional magnetic resonance imaging (MRI) findings included a large intra axial mass in the left frontal lobe that was T2 hyperintense and T1 hypointense centrally with a contrast-enhancing peripheral capsule and perilesional T2 hyperintensity. A restrictive pattern was present in diffusion-weighted imaging. Magnetic resonance spectroscopy demonstrated an increased amount of succinate, acetate, amino acids, lipids; minimal amounts of lactate; and decreased amounts of N-acetyl aspartate and choline. A cerebral abscess due to Trueperella pyogenes was confirmed from necropsy and tissue culture.

In vivo diagnosis of tick-borne encephalitis is difficult due to high seroprevalence and rapid viral clearance, limiting detection of antibodies in blood and cerebrospinal fluid. Magnetic resonance imaging (MRI) characteristics of tick-borne encephalitis have been reported, however MRI studies can also be negative despite the presence of neurologic signs. Magnetic resonance spectroscopy (

An eight-year-old, neutered male labrador was presented with recent recurrent vestibular episodes. MRI was consistent with multiple lacunar ischaemic infarcts in the thalamus and medulla oblongata. The imaging diagnosis was supported by a markedly elevated D-dimer concentration. Despite a comprehensive diagnostic workup (including fine needle cytology of cutaneous and subcutaneous nodules, complete bloodwork, urinalysis, thoracic and abdominal imaging, cerebrospinal fluid analysis, serial blood pressure measurements, echocardiography, electrocardiography and brainstem auditory evoked response testing), no underlying cause was found. After a partial response to 2 mg/kg clopidogrel once a day and 1 mg/kg prednisolone once a day, the dog acutely deteriorated and repeated MRI of the brain revealed an intra-axial haemorrhagic mass. Euthanasia was elected and postmortem examination revealed the presence of an intravascular null-cell lymphoma, exclusively in the central nervous system. Intravascular lymphoma is rare, difficult to diagnose ante-mortem and reports in veterinary literature are few.

Pancreatic enzyme replacement therapy (PERT) is essential for maintaining adequate nutrition in children with exocrine pancreatic insufficiency (EPI) due to cystic fibrosis (CF). The US Food and Drug Administration regulations now require all PERT products to undergo clinical efficacy and safety studies before they can be considered for marketing approval.This study was conducted to compare the efficacy of a new formulation of pancrelipase (pancreatin) delayed-release 12,000-lipase unit capsules with placebo in children with EPI due to CF.This was a multicenter, randomized, double-blind, placebo-controlled, 2-period crossover, superiority study of the new formulation of pancrelipase delayed-release 12,000-lipase unit capsules in children aged 7 to 11 years with CF and EPI. In each period, pancrelipase or identical placebo capsules were taken for 5 days. The primary outcome measure was the coefficient of fat absorption (CFA); secondary outcome measures were the coefficient of nitrogen absorption (CNA) and clinical symptoms. The latter were assessed based on patient-reported daily stool frequency, stool consistency (hard, formed/normal, soft, or watery), flatulence (none, mild, moderate, or severe), and abdominal pain (none, mild, moderate, or severe). Safety measures included vital signs, physical examinations, standard laboratory safety tests (hematology and biochemistry), and adverse events.Seventeen patients were randomized to treatment and 16 completed the study; 1 patient withdrew consent during the first treatment period and was not included in the efficacy analysis. Patients' median age was 8.0 years (range, 7-11 years); 12 patients (70.6%) were male. CFA values were significantly greater for pancrelipase compared with placebo, with least squares mean (SE) values of 82.8% (2.7%) and 47.4% (2.7%), respectively (P0.001). The results were similar for CNA, with mean values of 80.3% (3.2%) and 45.0% (3.2%) (P0.001). Pancrelipase treatment had significantly greater effects on CFA and CNA in patients with a placebo CFA50% than in those with a placebo CFA50% (both parameters, P0.001 and P = 0.008, respectively). Significant improvements in stool fat, weight, and nitrogen and a significant reduction in daily stool frequency were observed with pancrelipase compared with placebo (all, P0.001). Symptoms of EPI were less severe and remained relatively stable during pancrelipase treatment, but worsened slightly during receipt of placebo. Treatment-emergent adverse events were reported in 5 patients (29.4%) during receipt of pancrelipase and in 9 patients (56.3%) during receipt of placebo; these were predominantly gastrointestinal events. There were no discontinuations due to treatment-emergent adverse events and no serious adverse events.In this study in children with EPI due to CF, the new formulation of pancrelipase delayedrelease capsules was associated with improvements in CFA, CNA, stool properties, and EPI symptoms compared with placebo. Pancrelipase delayed-release capsules appeared to be well tolerated. ClinicalTrials.gov identifier: NCT00690820. (Clin Ther.

Central European tick-borne encephalomyelitis can be challenging to diagnose in dogs because the virus may not be detected in blood and cerebrospinal fluid (CSF) after the first viremic stage of the disease. The purpose of this retrospective case series study was to describe 3 Tesla magnetic resonance imaging (3T MRI) findings in a sample of dogs with a confirmed diagnosis of tick-borne encephalomyelitis. Dogs were included if they had neurological signs consistent with tick-borne encephalomyelitis, history of a stay in endemic areas for tick-borne encephalomyelitis virus, 3T MRI of the brain and/or spinal cord, cerebrospinal fluid changes compatible with viral infection and positive antibody titers in cerebrospinal fluid or pathologic confirmation of tick-borne encephalomyelitis. Twelve dogs met inclusion criteria. Ten out of 12 patients had 3T MRI lesions at the time of presentation. One patient had persistent lesions in follow-up MRI. The 3T MRI findings included bilateral and symmetrical gray matter distributed lesions involving the thalamus, hippocampus, brain stem, basal nuclei, and ventral horn on the spinal cord. All lesions were hyperintense in T2-weighted sequences compared to white matter, iso- to hypointense in T1-weighted, nonenhancing, and had minimal or no mass effect or perilesional edema. Six patients survived while the remaining six dogs were euthanized. Necropsy revealed neuronophagia and gliosis of the gray matter of the affected regions seen in 3T MRI, in addition to the cerebellum. Findings from the current study indicated that tick-borne encephalomyelitis should be included in the differential diagnosis list for dogs with the above described 3T MRI characteristics.

Background A plethora of treatment options have been described for canine meningoencephalitis of unknown origin (MUO), yet a gold standard has not been established. The aim of this prospective pilot study was to document the effect of a newly designed 30 Gray (Gy) radiation therapy (RT) protocol plus corticosteroids as treatment for focal and multifocal MUO, to monitor clinical and imaging changes during the course of the disease with conventional magnetic resonance imaging (MRI) and proton MR Spectroscopy (H-1 MRS) and to detect the occurrence of radiation related side effects. Results Six dogs (3 with focal and 3 with multifocal lesions) were included in the study. The RT protocol used consisted of 30 Gy in 10 fractions. The neurological status of all six dogs improved during RT, with 3 of 6 cases returning to a normal condition. One dog was euthanized early during follow-up (

Das Frühsommermeningoencephalitis (FSME) Virus ist endemisch in der Schweiz und verursacht Meningoencephalomyelitis beim Hund. Wir beschreiben hier einen Fall von FSME beim Hund mit Tetraparese und Atemlähmung. Die Magnetresonatztomographie zeigte intra-axiale bilateral symmetrische und hyperintense Läsionen in T2 gewichteten Sequenzen im Thalamus, den Basalkernen, der cerebralen weissen Substanz und dem Ventralhorn des Hals- Rückenmarks. Diese Bildgebungsbefunde sind vergleichbar mit Bildgebungsbefunden von humanen FSME Fällen. Die Läsionen im MRI und im Diffusionsgewichteten MRI korrelieren mit Bereichen von vasogenem Ödem in der Pathohistologie. In endemischen Gebieten sollte bei bilateral symmetrischen hyperintensen thalamischen Läsionen in T2 gewichteten Sequenzen FSME als Differentialdiagnose in Betracht gezogen werden., Tick borne encephalitis virus (TBE) is an endemic infectious agent in northeastern Switzerland causing mainly meningoencephalomyelitis in dogs. We report a canine case of tick born meningoencephalomyelitis resulting in flaccid tetraplegia and, subsequently, fatal respiratory failure. Magnetic resonance imaging (MRI) demonstrated intra-axial bilateral, symmetric, and hyperintense lesions in T2-weighted and Fluid Attenuated Inversion Recovery (FLAIR) sequences affecting thalamus, basal nuclei, cerebral white matter and ventral horns of the caudal cervical spine. These radiological findings overlap those described during flavivirus encephalitis affecting human beings. These lesions in MRI and diffusion weighted images correlated with areas of vasogenic edema detected histopathologically. In endemic regions, clinicians should be aware that bilateral, symmetrical hyperintense thalamic lesions in T2WI can be suggestive of flavivirus infection in dogs with encephalitis

Simvastatin and fenofibrate are frequently co-prescribed at staggered intervals for the treatment of dyslipidemia. Since a drug-drug interaction has been reported when the two drugs are given simultaneously, it is of clinical interest to know whether the interaction differs between simultaneous and staggered combinations. A study, assessing the impact of both combinations on the interaction, was conducted with 7-day treatment regimens using simvastatin 40 mg and fenofibrate 145 mg: (A) simvastatin only (evening), (B) simvastatin and fenofibrate (both in evening), and (C) simvastatin (evening) and fenofibrate (morning). Eighty-five healthy subjects received the respective treatments in a randomized, 3-way cross-over study. The pharmacokinetics of simvastatin and the active metabolite simvastatin acid were determined. There was a limited reduction in the AUC0-24h of simvastatin acid of 21 and 29% for simultaneous and staggered combination, respectively. The geometric mean AUC0-24h ratio of simvastatin acid for the two combined dosing regimens (B/C) and 90% confidence interval were 111% (102-121). The interaction apparently had no impact on lipid markers. The findings imply that the observed pharmacokinetic interaction is unlikely clinically relevant, and support the combined use of simvastatin and fenofibrate not only given at staggered interval but also given simultaneously.

A 2-month-old female goat was presented for depressed mental status and multifocal central neurologic signs 3 weeks after hot-iron disbudding. Conventional magnetic resonance imaging (MRI) findings included a large intra axial mass in the left frontal lobe that was T2 hyperintense and T1 hypointense centrally with a contrast-enhancing peripheral capsule and perilesional T2 hyperintensity. A restrictive pattern was present in diffusion-weighted imaging. Magnetic resonance spectroscopy demonstrated an increased amount of succinate, acetate, amino acids, lipids; minimal amounts of lactate; and decreased amounts of N-acetyl aspartate and choline. A cerebral abscess due to Trueperella pyogenes was confirmed from necropsy and tissue culture.

A new di-manganese complex with "back-to-back" 1,4-bis(2,2':6,2''-terpyridin-4'-yl) benzene ligation has been synthesized and characterised by a variety of techniques. The back-to-back ligation presents a novel new mononuclear manganese catalytic centre that functions as a heterogeneous catalysis for the evolution of oxygen in the presence of an exogenous oxidant. We discuss the synthesis and spectroscopic characterizations of this complex and propose a mechanism for oxygen evolution activity of the compound in the presence of oxone. The di-manganese complex also shows efficient and selective catalytic oxidation of sulfides in the presence of H(2)O(2). Density functional theory calculations were used to assess the structural optimization of the complex and a proposed reaction pathway with oxone. The calculations show that middle benzene ring is distorted respect to both of metallic centers, and this in turn leads to negligible resonance of electrons between two sides of complex. The calculations also indicate the unpaired electron located on oxyl-ligand emphasizes the radical mechanism of water oxidation for the system.